The proposed research has two objectives: 1) to investigate the genetic and physiological control mechanisms of tetrahydrofolate metabolism; 2) to determine the role of proteases in the metabolism and differentiation of yeast. Mutants altered in THFA metabolism will be analyzed genetically and biochemically. The THFA interconversion enzymes will be purified to see whether they occur in an enzyme aggregate. The intracellular localization of these enzymes will be determined. Mutants with alterations in the function or regulation of proteases will be isolated and characterized both with respect to genetics and biochemistry. The consequences to the cell of such alterations in protease function will be examined. This research should contribute to our understanding of regulatory mechanisms underlying transport of proteins through membranes, and may contribute to our understanding of the mechanisms governing transitions between cell states (meiosis and mitosis). BIBLIOGRAPHIC REFERENCES: Cohen, Bruce M. and Elizabeth W. Jones, 1976. New map location of ilvO in Escherichia coli. Genetics (in press).